# Analysis of Gene, Environment, and Sex Interaction in the Development of Autistic-like Phenotype in Mice

## TL;DR

This study explores how genes, environment, and sex interact to influence autistic-like behaviors in mice, revealing that these factors work together in specific ways.

## Contribution

The study demonstrates that genetic predisposition, sex, and environmental factors interact to influence specific autistic-like behaviors in mice.

## Key findings

- CNTNAP2 knockout, sex, and maternal immune activation had additive effects on repetitive and social behaviors in offspring.
- Working memory and sensory gating were not affected by these factors.
- The interaction of genetics, sex, and environment influences autistic-like phenotypes in a behavior-specific manner.

## Abstract

Autism Spectrum Disorder (ASD) is a developmental disorder that manifests a broad variability of phenotypes. The underlying factors contributing to the diverse presentation of autistic phenotypes remain poorly understood. Studies have shown that environmental and genetic factors could contribute to ASD. Additionally, there is a sex bias in the disorder, where the prevalence in males is higher than in females. But it is still unknown how exposure to similar risk factors can lead to different phenotypes. The three-hit theory states that the vulnerability of an individual to develop ASD is modulated by the interplay between genetic predisposition, sex, and environmental insults. To better understand this phenomenon, we investigated whether an environmental insult, via maternal immune activation (MIA) during pregnancy could influence the development of the autistic-like phenotype in a genetically predisposed mouse strain, contactin-associated protein-like 2 (CNTNAP2) knockout. CNTNAP2 knockout, sex, and maternal immune activation had significantly additive effects on repetitive/stereotyped and social behavior in the offspring, while working memory and sensory gating were not affected by hits. These results indicate that genetics, sex, and environment interact to influence autistic-like phenotypes in a behavior-specific manner.